Sunday, July 17, 2016

Spore-Forming Probiotics - The Better Probiotics? Review

Sauerkraut is one of the best known probiotic foods, but there's more: Kefir & yogurt, kimchi, kombucha, miso, pickles, apple cidar vinegar, and - as discussed recently - raw cheese.
I found out rather accidentally that there is a potentially relevant difference between "probiotics" and "spore-forming probiotics". Relevant enough for me to believe that you should learn about this difference, as well. After all, it seems as if the spores, you will probably only know from anthrax, provide a solution to the #1 major obstacle of efficient probiotic therapies: the destruction and digestion of the life bacteria before they even reach their destination in the colon.

If we go by the WHO definition probiotics are "live microorganisms which, when administered in adequate amounts, confer a health benefit on the host" (FAO/WHO. 2002) - spore-forming or not, stable or unstable freeze dried or encapsulated.
You can learn more about the gut & your health at the SuppVersity

Bugs Dictate What You Crave

Sweeteners & Your Gut

Foods, Not Ma- cros for the Gut

Lactulose For Gut & Health

Probiotics Don't Cut Body Fat

The Macrobiotic MaPi2.0 Diet
Not all of them, however, share the often mourned lack of shelf-life and susceptibility to breakdown in the acidic milieu of the upper gastroinstestinal tract. This is why chances are that only a very small percentage of your probiotic supplement is (a) viable at the end of its shelf-life and (b) able to transit the ph-barrier of your upper gastrointestinal tract.

Figure 1: Illustration of the process of spore-formation from a presentation by Marthese Azzopardi.
The most commonly available alternative that will guarantee both, i.e. a long shelf-life and successful transit of the intestinal pH barrier is "Bacillus coagulans", a gram-positive, spore-forming, microaerophilic, lactic-acid producing bacillus that is not - by definition - part of the Lactobacillus genus; and that despite the fact that it is still often falsely referred to and even labelled as "Lactibacillus sporogenes"... needless to say: you also have to distinguish coagulans from unfortunately better-known spores such as ahtrax, the 1,300 year old lethal weapon of terror.

What's special about spore-forming probiotics?

B. coagulans and other spore-forming probiotics protect themselves with a unique spore-like protein coating, "which allows it to survive stomach acid, reach the small intestine, germinate, and multiply" (Jurenka. 2012). As Jurenka et al. point out in their 2012 review of the literature ...
"[...] B. coagulans arrives in the stomach in its spore form, where it is exposed to the stomach's churning action and acidic pH that causes the spore coating to absorb water, swell, and begin the germination process. Upon arrival in the duodenum, the spores germinate and multiply rapidly" (Jurenka. 2012). 
Ghandi et al. have estimate the average duration of time between oral consumption and germination to be roughly 4-6 hours (Gandhi. 1988). This, alone, obviously isn't a major advantage. Rather than the time to germination, it is their ability to germinate in the intestinal tract, at all, that makes them stand out of the probiotic crowd. With a 85% survival rate (meaning 85% of the starting material reaching the intestinal tract intact), B coagulans is the #1 among easily obtainable probiotics when it comes to becoming metabolically active in the intestines (other species such as lactobacilli require special treatment like micro-encapsulation to achieve similar absorption rates | Kailasapathy. 2000).

Figure 2: Many scientists believe that our battle against commensurable bacteria is the reason for many modern diseases (auto-)immune diseases.
Once they are there, B. cuagulans does practically the same as the often hailed lactobacillii strains: it produces levorotatory L(+)lactic acid (Ong. 2016), the form most readily metabolized in glycogen synthesis by the body (i.e., the isomeric form that would not be expected to contribute to metabolic acidosis).

What is particularly intriguing, though, is that they do so without superseeding their 'regular' cousins, because the colonization is transient and the spores of B. coagulans are excreted slowly via the feces for approximately seven days after discontinuation of administration (Majeed. 1998).

Wait - If it doesn't stay, how does it work?

As Jurenka et al. highlight in their previously referenced review, B. cuagulans will, despite the transient of this organism in the digestive tract, "produce a shift in the intestinal environment in support of a complex gastrointestinal flora" (Jurenka. 2012). In pigs which constitute the best animal model for the human digestive tract, for example, they have been shown to reduce 'bad' bacteria as effectively as antibiotics (Adami. 1999) - and they do that without negative impact on any of the 'good' bacteria which makes them the ideal , and meanwhile scientifically proven - alternative for the chronic administration of antibiotics in livestock breeding (Zhenya. 2015).
Can't these bacilli harm you? Toxicological safety assessments for B. coagulans indicate no mutagenic, clastogenic, or genotoxic effects. Results of an acute and 90-day subchronic oral toxicity study in rats yielded a No Adverse Effects Level (NOEL) greater than 1,000 mg/kg per day (Endres. 2009). As Jurenka et al. point out in their review, Endres et al. used B. coagulans at a concentration equal to 95.2 x 10^11, i.e. almost 100 billion CFU for a 70-kg human - that's 30x more than the typical upper limit you will find in supplements which are usually dosed between 100 million an 3 billion CFUs daily. Furthermore, "in humans, adverse reactions following supplementation have not been reported in the peer-reviewed literature" - and this includes even minor side effects such as bloating. More recently human safety data for another strain has been published (Majeed. 2016c).
This effect is presumably mediated by improvements of the gastrointestinal ecology, replenishing the quantity of desirable obligate microorganisms and antagonizing pathogenic microbes (Jurenka. 2012), which, in turn, is a result of the increased production of bacteriocins, bacteriocin-like substances, which are both germ-specific natural antibiotics, as well as short-chain fatty acids that nourish the colonic mucosa (Mandel. 2010). This and direct influence on local and systemic inflammation that have been observed in vitro and - as in the case of the arthritic subjects in Mandel's 2010 study - in vivo, explains the repeatedly observed effects of B. coagulans on both, gastrointestinal disorders (local inflammation) and metabolic disease & inflammatory diseases such as arthritis.

Proven health benefits of B. coagulans, the most widely available form of spore-forming probiotics (there are different strains available and there's insufficient evidence to compare their efficacy, though) that have been documented in animal and human studies and summarized in reviews are similar to what you already have seen with classic probiotics:
  • improved digestion, esp. of lactose, because B. coagulans shows [beta]-galactosidase (lactase) activity in vitro and may also have lactic acid dehydrogenase activity, thereby enhancing the digestibility of lactose in those who are lactose intolerant (Jurenka. 2012) 
  • improved cholesterol levels, because B. coagulans assimilates and incorporates cholesterol into its cellular structure, binds cholesterol in the gut, and may inhibit the cholesterol-producing enzyme HMG-CoA reductase | Mohan. 1990)
    Figure 3: As early as in 1990, Mohan et al. observed that the provision of "only" 360 million CFU of B. coagulans can significantly improve the cholesterol profile of  17 patients with type II hyperlipidemia (Mohan. 1990).
  • promotion of a healthy, balanced microbiome (+ all downstream health benefits), especially after antibiotic treatments and in the aging population in whom the prevalence of 'good' bacteria declines (Nyangale. 2015), because of B. cuagulans ability to prevent and counter dysbiosis, i.e. the over-growth of pathogenic microorganisms, battle irritable bowel syndeome (IBS), prevent antibiotic-associated or regular diarrhea (duration of diarrhea in kids is reduced by 12% | Dutta. 2011) and + flatulence (Kalman. 2009) and help the body cope with viral attacks (e.g. influenca; see Baron. 2009)
    Figure 4: Compared to regular probiotics B. coagulans is surprisingly effective at low doses of 5 million CFU when it comes to managing diarrhea in IBS patients (Majeed. 2016a).
  • athletic performance can be enhanced by B coagulans' ability to reduces indices of muscle damage, increases recovery and may maintain athletic performance after muscle damaging exercise (Jäger. 2015) - at least according to a recent study in which 30 healthy recreationally-trained males (mean+/-SD; age: 21.5 ± 2.8 years; height: 177.4 ± 8.0 cm; weight: 89.7 ± 28.2 kg) were randomly assigned to consume either 20 g of casein (Control = CON) or 20 g of casein plus probiotic (500M CFU | BC30) twice daily in a crossover, diet-controlled design for a two-week time period.
    Figure 5: In recreationally trained subjects, supplementing with B. coagulans prevents muscle damage and enhances subjective and objective measures of recovery from hitting the weights (Jäger. 2015).
    Subjects performed a damaging exercise bout consisting of 10 sets × 10 repetitions unilateral leg press at 70% 1 RM with 1 minute rest, one legged - leg extension (5 sets × 12 reps), and rear foot elevated split squat 5 sets × 12 reps with one minute rest at baseline and after two weeks of supplementation. Athletic performance consisting of peak power (Wingate 10 sec Peak Power Assessment at 7.5% BW at 175RPM threshold loaded drop), vertical jump power (Tendo unit, single-leg jump), and 1-RM single-leg press; and muscle damage was analyzed by muscle swelling (ultrasonography) and blood draws (creatine kinase (CK), blood urea nitrogen (BUN)) were taken at baseline (pre-supplementation) and 48 hours after damaging exercise bout. Perceptual measures (perceived recovery, soreness) were taken before, 24, 48 and 72 hours after exercise.

    The results are quite convincing: (1) the supplement significantly increased recovery at 24 and 72 hours, and decreased soreness at 72 hours post exercise in comparison to CON; and that's based on perceptual measures and (2) reduced increase in CK (CON: +266.8%, p = 0.0002; BC30: +137.7%, p = 0.01), as well as (3) preserved athletic performance in in BC30 (+10.1 watts, +1.7%) vs. CON (Wingate Peak Power; CON: (-39.8 watts, - 5.3%, p = 0.03).
  • women's health, when administered locally, B. coagulans have also been shown to be an anti-biotic alternative for women suffering from non-specific vaginitis (Shirodkar. 1980) - simply eating them will yet obviously not necessarily have that effect, ladies
Now all these are nice to have, but what my be of even greater importance is the fact that their resiliance makes B. coagulans the ideal addon to commercially available foods (even in liquids the bacteria will survive 6-24 months (!) | Majeed. 2016b), where their downstream effects on your metabolism (think of the microbiome <> diabesity connection) may help us control the obesity and diabetes epidemic... what? Oh, yes! There's an emphasis on "may", whether this is actually going to be the case will have to be confirmed in future studies, obviously ;-)
Yes, diet may affect your microbiome. Whether the changes are (a) relevant or (b) irrelevant is yet as questionable as whether the changes the scientists observed will (i) have a negative (ii) a positive or (iii) no effect | learn more.
So, you better take spore-forming vs. 'normal' probiotics? Well, I guess it would be too early to say that, but the fact that Russian scientists report that B. coagulans treatment in conjunction with traditional probiotics results in 20- to 30-percent higher treatment efficacy in humans with bacterial dysbiosis than traditional probiotics such as Lactobacillus acidophilus or Bifidobacteria alone (Voĭchishina. 1991). Since neither I nor one of the reviews I have read had access to an English version of Voĭchishina's paper, I cannot tell you whether the design allows any conclusions as to whether it is the combination of both or simple the addition of B. cougulans that is responsible for the 20-30% increase in efficacy.

In view of the fact that respective supplements are - in contrast to what you may think now - not extremely expensive and considering the fact that dosages as low as 100 million CFU have been shown to have significant health effects, it may not hurt to give B. cuagulans, which is currently the only easily obtainable sporeforming probiotic a try (don't ask me about the exact strain, though, there is insufficient evidence to say which one is best and if they even have sign. different health effects) - especially if you're having issues with your digestive tract: 30 days and if it doesn't work, you can still drop it | Comment on Facebook!
  • Adami, Annunciata, and Valeria Cavazzoni. "Occurrence of selected bacterial groups in the faeces of piglets fed with Bacillus coagulans as probiotic." Journal of basic microbiology 39.1 (1999): 3-10.
  • Baron, Mira. "Original research: A patented strain of bacillus coagulans increased immune response to viral challenge." Postgraduate medicine 121.2 (2009): 114-118.
  • Dutta, Phalguni, et al. "Randomised controlled clinical trial of Lactobacillus sporogenes (Bacillus coagulans), used as probiotic in clinical practice, on acute watery diarrhoea in children." Tropical Medicine & International Health 16.5 (2011): 555-561.
  • FAO/WHO Joint Working Group Report on Drafting Guidelines for the Evaluation of Probiotics in Food. London, Ontario, Canada; April 30 and May 1, 2002.
  • Gandhi, A. B. "Lactobacillus sporogenes, an advancement in Lactobacillus therapy." The Eastern Pharmacist (1988): 41-43.
  • Jäger, Ralf, et al. "Effects of probiotic supplementation on markers of skeletal muscle damage, perceived recovery and athletic performance after an intense single leg training bout." Journal of the International Society of Sports Nutrition 12.Suppl 1 (2015): P36.
  • Jurenka, Julie S. "Bacillus coagulans." Altern. Med. Rev 17 (2012): 76-81.
  • Kailasapathy, Kaila, and James Chin. "Survival and therapeutic potential of probiotic organisms with reference to Lactobacillus acidophilus and Bifidobacterium spp." Immunology and Cell Biology 78.1 (2000): 80-88.
  • Kalman, Douglas S., et al. "A prospective, randomized, double-blind, placebo-controlled parallel-group dual site trial to evaluate the effects of a Bacillus coagulans-based product on functional intestinal gas symptoms." BMC gastroenterology 9.1 (2009): 1.
  • Majeed, Muhammed, et al. "Bacillus coagulans MTCC 5856 supplementation in the management of diarrhea predominant Irritable Bowel Syndrome: a double blind randomized placebo controlled pilot clinical study." Nutrition journal 15.1 (2016a): 1.
  • Majeed, Muhammed, et al. "Evaluation of the stability of Bacillus coagulans MTCC 5856 during processing and storage of functional foods." International Journal of Food Science & Technology (2016b).
  • Majeed, Muhammed, et al. "A Double-Blind, Placebo-Controlled, Parallel Study Evaluating the Safety of Bacillus coagulans MTCC 5856 in Healthy Individuals." Journal of Clinical Toxicology 2016 (2016c).
  • Mandel, David R., Katy Eichas, and Judith Holmes. "Bacillus coagulans: a viable adjunct therapy for relieving symptoms of rheumatoid arthritis according to a randomized, controlled trial." BMC complementary and alternative medicine 10.1 (2010): 1.
  • Mohan, J. C., R. Arora, and M. Khalilullah. "Preliminary observations on effect of Lactobacillus sporogenes on serum lipid levels in hypercholesterolemic patients." The Indian journal of medical research 92 (1990): 431-432.
  • Nyangale, Edna P., et al. "Bacillus coagulans GBI-30, 6086 modulates Faecalibacterium prausnitzii in older men and women." The Journal of nutrition 145.7 (2015): 1446-1452.
  • Ong, Shufen Angeline, Zhi Jian Ng, and Jin Chuan Wu. "Production of high concentration of l-lactic acid from cellobiose by thermophilic Bacillus coagulans WCP10-4." Applied microbiology and biotechnology (2016): 1-8.
  • Shirodkar, N. V., et al. "Multi-Centre Clinical Assessment Myconip Vaginal Tablets-in Non-Specific Vaginitis." The Indian Practitioner 33.4 (1980): 207-210.
  • Zhenya, Zhai, et al. "Effect of dietary supplementation with dimethyl potassium and Bacillus coagulans instead of antibiotics on growth performance and immune parameters in weaned piglets [J]." Feed Industry 12 (2015): 002.